The understanding of the events following various types of cell injury is crucial to the development of our knowledge concerning the pathogenesis, treatment and prevention of human diseases. As has now become evident, all disease states are most meaningfully expressed at the cellular and subcellular levels with such changes forming the basis of the physiological and morphological alterations observed. Based on studies we and others have performed through the years, it is our hypothesis that many of the cellular changes which lead the cell from normal to irreversibly injured are initiated and modified by primary and/or secondary effects of ion redistributions taking place between the cell and the extracellular compartment and between various compartments in the cell. Although the clinical effects of this syndrome have been well characterized in the literature, specific aspects concerning effects at the cellular and subcellular levels need to be further clarified as do the effects of various agents currently under investigation as possible therapeutic agents. Therefore, the aim of this proposal is to characterize the cellular and subcellular effects of bacteremic shock in the liver using an in vivo rat model and to compare these results to the in vitro model. This will be accomplished by physiological monitoring of the in vivo model and followed by morphological and biochemical observations in both models. Such data will elucidate changes at the subcellular level in cell membranes such as the plasma membrane, mitochondria and endoplasmic reticulum. Most importantly, the use of x-ray microanalysis will enable us to determine the nature and pattern of the occurrence of ion shifts following this injury and to correlate these with the morphological and biochemical data. The same methodology will then be used to monitor the effects of various agents aimed at altering the course of this injury and to correlate their efficacy with effects on ion distributions and survival rates. Data gathered from such experimentation should lead to a more refined understanding of the many phenomena which exist in this complex syndrome and to improved preventive or post-injury interventions.